Angulin proteins ILDR1 and ILDR2 regulate alternative pre-mRNA splicing through binding to splicing factors TRA2A, TRA2B, or SRSF1

Liu, Yueyue; Nie, Hongyun; Liu, Chengcheng; Zhai, Xiaoyan; Sang, Qing; Wang, Yanfei; Shi, De-Li; Wang, Lei; Xu, Zhigang

doi:10.1038/s41598-017-07530-z

Cited by 19 publications

(25 citation statements)

References 51 publications

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“…Mutations of ILDR1 gene are associated with autosomal recessive hearing impairment DFNB42, and knockout of Ildr1 gene in mice leads to degeneration of mechanosensory cochlear hair cells, resulting in hearing loss [22]. Our previous data showed that ILDR1 interacts with a series of splicing factors and regulates alternative splicing [23]. In the present work, we demonstrate that ILDR1 promotes IAV replication through interacting with PLSCR1.…”

Section: Introductionsupporting

confidence: 63%

ILDR1 Promotes Influenza a Virus Replication Through Binding to PLSCR1

Liu

Xie

et al. 2021

Preprint

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As a natural antiviral regulator, phospholipid scramblase 1 (PLSCR1) has been shown to inhibit influenza virus replication in infected cells through interacting with NP of influenza A virus (IAV). But its antiviral function as well as the underlying regulatory mechanism has not been examined in vivo. In the present work, we show that PLSCR1 expression is decreased in H1N1 SIV-infected mice, and Plscr1−/−mice are more susceptible to H1N1 SIV infection. By performing yeast two-hybrid screening, we identified immunoglobulin-like domain-containing receptor 1 (ILDR1) as a novel PLSCR1-binding partner. ILDR1 is highly expressed in the lungs, and its expression level is increased after virus infection. Interestingly, ILDR1 could not directly interact with virus NP protein, but could combine with PLSCR1 competitively. Our data indicates that there is a previously unidentified PLSCR1-ILDR1-NP regulatory pathway playing a vital role in limiting IAV infection, which provides novel insights into IAV-host interactions.

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Section: Introductionsupporting

confidence: 63%

ILDR1 Promotes Influenza a Virus Replication Through Binding to PLSCR1

Liu

Xie

et al. 2021

Preprint

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“…Splicing factors SRRM4, SFSWAP, and ESRP1 play important roles in the inner ear, albeit none of them has been shown to regulate the alternative splicing of Cdh23 exon 68 [ 18 – 20 ]. We previously showed that deafness-related protein ILDR1 and its homolog ILDR2 regulate alternative splicing through binding to splicing factors TRA2A, TRA2B, and SRSF1 [ 21 ]. We also found that RNA-binding protein RBM24 is specifically expressed in the hair cells [ 22 ].…”

Section: Resultsmentioning

confidence: 99%

Alternative Splicing of Cdh23 Exon 68 Is Regulated by RBM24, RBM38, and PTBP1

Ren

et al. 2020

Neural Plasticity

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Alternative splicing plays a pivotal role in modulating the function of eukaryotic proteins. In the inner ear, many genes undergo alternative splicing, and errors in this process lead to hearing loss. Cadherin 23 (CDH23) forms part of the so-called tip links, which are indispensable for mechanoelectrical transduction (MET) in the hair cells. Cdh23 gene contains 69 exons, and exon 68 is subjected to alternative splicing. Exon 68 of the Cdh23 gene is spliced into its mRNA only in a few cell types including hair cells. The mechanism responsible for the alternative splicing of Cdh23 exon 68 remains elusive. In the present work, we performed a cell-based screening to look for splicing factors that regulate the splicing of Cdh23 exon 68. RBM24 and RBM38 were identified to enhance the inclusion of Cdh23 exon 68. The splicing of Cdh23 exon 68 is affected in Rbm24 knockdown or knockout cells. Moreover, we also found that PTBP1 inhibits the inclusion of Cdh23 exon 68. Taken together, we show here that alternative splicing of Cdh23 exon 68 is regulated by RBM24, RBM38, and PTBP1.

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“…The yeast two-hybrid screen was performed as previously described [ 26 – 28 ]. Briefly, yeast strain AH109 (Clontech) was sequentially transformed with the bait plasmid and a chicken cochlear cDNA library in the HybriZAP two-hybrid vector [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

Identification of Binding Partners of Deafness-Related Protein PDZD7

Ren

Chen

et al. 2018

Neural Plasticity

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PDZD7 is an important deafness gene, whose mutations are associated with syndromic and nonsyndromic hearing loss. PDZD7 contains multiple PDZ domains that are essential for organizing various proteins into protein complex. Several PDZD7-binding proteins have been identified, including usherin, ADGRV1, whirlin, harmonin, SANS, and MYO7A, all belonging to USH proteins. Here, we report the identification of novel PDZD7-binding partners through yeast two-hybrid screening using the first two PDZ domains of PDZD7 as bait. Eleven proteins were identified, most of which have not been reported as PDZD7-binding partners before. Among the identified proteins, ADGRV1, gelsolin, and β-catenin have been shown to play important roles in hearing, whereas the functions of other proteins in the inner ear remain elusive. We confirmed the expression of one candidate PDZD7-binding protein, CADM1, in the mouse inner ear and evaluated the auditory function of Cadm1 knockout mice by performing auditory brainstem response (ABR) measurement. Unexpectedly, Cadm1 knockout mice show normal hearing threshold, which might be explained by the possible compensation by its homologs that are also expressed in the inner ear. Taken together, our work identified several novel PDZD7-binding proteins, which will help us to further understand the role of PDZD7 in hearing transduction.

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Angulin proteins ILDR1 and ILDR2 regulate alternative pre-mRNA splicing through binding to splicing factors TRA2A, TRA2B, or SRSF1

Cited by 19 publications

References 51 publications

ILDR1 Promotes Influenza a Virus Replication Through Binding to PLSCR1

ILDR1 Promotes Influenza a Virus Replication Through Binding to PLSCR1

Alternative Splicing of Cdh23 Exon 68 Is Regulated by RBM24, RBM38, and PTBP1

Identification of Binding Partners of Deafness-Related Protein PDZD7

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